Efficacy of γ-linolenic Acid and Thioctic Acid in Patients With Diabetic Neuropathy

Diabetic Neuropathy Clinical Trial

Official title:

A 12-week, Multi-center, Randomized, Double-blind, Double Dummy, Parallel Clinical Trial to Compare the Efficacy of γ-linolenic Acid and Thioctic Acid in Patients With Diabetic Neuropathy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03914404
• Other study ID #: DLB-DN-EVOP
• Status: Completed
• Phase: Phase 4
• Start date: January 26, 2016
• Est. completion date: July 25, 2018

Study information

• Verified date: April 2019
• Source: Chonbuk National University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study was a 12-week, multi-center, randomized, double-blind, double dummy, parallel clinical trial to compare the efficacy of γ-linolenic acid and Thioctic acid in patients with diabetic neuropathy.

Description:

This study evaluated non-inferiority about the efficacy and safety of γ-linolenic acid (Evoprim soft capsule) through patients with diabetic neuropathy were compared γ-linolenic acid (Evoprim soft capsule) and Thioctic acid(LipoA HR Tab. 600mg) using double-blind, double dummy clinical trials. First outcome measures are Visual Analog Scale(VAS) and Total Symptom Score(TSS), secondary outcome measures are Michigan Neuropathy Screening Instrument(MNSI), Current perception Threshold(CPT), Modified Brief Pain Inventory-diabetic polyneuropathy(Modified BPI-DPN) and EuroQol-5 Dimensions(EQ 5D).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: July 25, 2018
• Est. primary completion date: March 30, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 75 Years

Eligibility

Inclusion Criteria:

• Patients who were between 20 years and 75 years at screening

• Patients who were diagnosed with type 2 diabetes and whose HbA1c levels were less than 11% at screening

• Patients with a score of 4 or more on the Visual Analogue Score(VAS)

• One or more of the following items

• If the physical examination score of the Michigan Neuropathy Screening Instrument Score (MNSI) is more than 2 points at the initial screening

• type 2 diabetic patient who complained one or more of pain, burning sensation, numbness, and sensory loss and measured the current perception threshold (CPT) of the peroneal nerve at three frequencies (2000Hz, 250Hz, 5Hz) Anyone whose diabetes mellitus has been diagnosed as diabetic neuropathy

• Patients who decided to voluntarily participate in clinical trials and agreed in writing

Exclusion Criteria:

• Peripheral neuropathy caused by other causes other than diabetes

• Those are suffering from other painful conditions that are so severe that diabetic neuropathy can not be assessed

• If you have a progressive or degenerative neurological disorder

• Patients with a systolic blood pressure(SBP)= 160 mmHg or = 100 mmHg or a diastolic blood pressure(DBP) = 95 mmHg or = 60 mmHg

• Patients who were positive for human immunodeficiency virus (HIV), hepatitis B (HBV), or hepatitis C (HCV) test

• patients with liver dysfunction (ALT / AST> 3 times the upper limit of normal)

• Patients with renal dysfunction (Serum creatine> 2.0 mg / dl)

• Patients with thyroid dysfunction (Thyroid and anti-thyroid medications may be included in this study if they are maintained in normal state.)

• Patients with amputation (including toes) or infections of the lower extremities

• The following diseases are clinically significant patients

• Unstable coronary artery disease or peripheral vascular disease

• Liver, kidney, lung, hematologic disease

• Cancer (within 5 years if possible)

• Patients who have suicide attempts or suicidal tendencies and who have a psychiatric history within 6 months before starting the trial

• Patients with substance abuse or chronic alcohol abuse within 2 years prior to taking the test

• Patients who received intravenous steroid injection or topical anesthetic injection within 2 months before participating in the study

• Patients who participated in other studies within 4 weeks before participating in the trial, or who are currently taking medication for other research

• Screening After randomization for 2 weeks (pause period) before screening, antipsychotics, antipsychotics, sleep depressants, antidepressants, antiepileptics, muscle relaxants, analgesics (narcotic analgesics, NSAIDs, tramadol etc.) Patients who received capsaicin or who received percutaneous electrical nerve stimulation therapy (TENS) or acupuncture

• Patients with a history of hypersensitivity or clinically significant hypersensitivity reactions to this drug substance and soybean oil, soy or peanut

• Patients with clinically significant skin disease or severe skin irritability

• Pregnant or lactating women

• patients suffering from schizophrenia or those who are treated with chloropromazine, mesoridazine, thioridazine, fluphenazine, perphenazine, trifluoperazine, haloperidol (haloperidol), loxapine (loxapine) and other drugs known to cause epileptic seizures

• In addition to the above items, patients who are deemed inappropriate by clinical trial researchers

Related Conditions & MeSH terms

• Diabetic Neuropathies
• Diabetic Neuropathy

Intervention

Drug:
• ?-linoleic acid and placebo(Thioctic Acid)
?-linoleic acid (Evoprim soft capsule) twice a day and 4 capsules at a time. Thioctic Acid(LipoA HR Tab. 600mg) placebo once a day and 1 tablet at a time.
• Thioctic Acid and placebo(?-linoleic acid)
Thioctic Acid(LipoA HR Tab. 600mg) once a day and 1 tablet at a time. ?-linoleic acid (Evoprim soft capsule) placebo twice a day and 4 capsules at a time.

Locations

Country	Name	City	State
Korea, Republic of	Sejong hospital	Bucheon	Gyeonggi
Korea, Republic of	Soon chun hyang university hospital cheonan	Cheonan	South Chungcheong Province
Korea, Republic of	Daegu Catholic University Medical Center	Daegu
Korea, Republic of	Dongguk university gyeongju hospital	Gyeongju	North Gyeongsang-do
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Obesity Research Center of Chonbuk National University	Jeonju	Jeollabuk-do
Korea, Republic of	Pusan National University Hospital	Pusan
Korea, Republic of	Inje university sanggye paik hospital	Seoul
Korea, Republic of	The catholic university of korea seoul st. mary's hospital	Seoul
Korea, Republic of	The catholic university of korea Yeouido st. mary's hospital	Seoul
Korea, Republic of	Yonsei univesity severance hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Chonbuk National University Hospital

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes of Visual Analog Scale(VAS)	The Visual Analog Scale(VAS) score is 0 point for no symptom, 10 points for the most severe symptom, and the patient is asked to mark the degree of subjective pain symptoms as an integer.	12 weeks
Primary	Changes of Total Symptom Score(TSS)	Total Symptom Score(TSS) classifies diabetic neuropathy symptoms into four categories (pain, burning pain, paresthesia, numbness). The frequency (Occasional, Frequent, Continuous) and symptom intensity (Absent, Slight, Moderate, Severe) are calculated through each question and the score is obtained according to the visual analog scale. It is calculated from 0 point up to 14.64 points.	12 weeks
Secondary	Changes of Michigan Neuropathy Screening Instrument(MNSIQ)	A 15-item questionnaire (MNSIQ) is used to assess deformation, infection, skin thickening of the skin's stratum corneum, and ulcers.; MNSIQ was designed to screen for diabetic neuropathy through questionnaires on 15 questions that are related to neuropathic symptoms (pain, temperature, and sensation). Two of 15 (number 4 and 10) are vascular symptoms and are excluded from the total score regardless of the results. If you answered 'No' to questions 7 and 13, you will get 1 point. In the end, scores ranging from 0 to 13 indicate that the higher the score, the more severe the neuropathic symptoms.	12 weeks
Secondary	Changes of Michigan Neuropathy Screening Instrument(MNSIE)	A foot test (MNSIE) is used to assess deformation, infection, skin thickening of the skin's stratum corneum, and ulcers.; MNSIE evaluates foot shape, foot ulceration, ankle reflex, sense of vibration of big toe, monofilament right and left. The score ranges from point 0 to 10, and when the score is above 2, it is diagnosed as neuropathy.	12 weeks
Secondary	Changes of Current perception Threshold(CPT)	Sensory nerve conduction threshold (SNCT) is a unique method for evaluating all three sensory neurons (small unmyelinated fibers, small myelinated fibers, and large myelinated fibers) that make up more than 90% of sensory nerves. It seems to be possible to objectively evaluate sensory nerve of small fiber which recovered early in diabetic neuropathy(Using neurometer).	12 weeks
Secondary	Changes of Modified Brief Pain Inventory-diabetic polyneuropathy(Modified BPI-DPN)	Modified Brief Pain Inventory-diabetic polyneuropathy(Modified BPI-DPN) displays the pain area on the human figure, the number of pain sites, treatment of pain, and pain medication.; Pain severity refers to the pain sensation- identification aspect (pain threshold). The worst pain, the least pain, the pain average, and the pain now for the last 24 hours are displayed on the 10-point scale (0 points: none, ~ 10 Point: too big to imagine). Pain interference is the emotional-synchronous aspect of pain (pain tolerance). It classifies general activity, mood, walking, working, relationship, sleep and enjoyment of life, and use the 10-point scale (0 points: none to 10 points: completely disturbed).	12 weeks
Secondary	Changes of EuroQol-5 Dimensions(EQ 5D)	EQ-5D index = 1 - (0.050 + 0.096 M2 + 0.418 x M3 + 0.046 x SC2 + 0.13 x SC3 + 0.051 x UA2 + 0.028 x UA3 + 0.037 x PD2 + 0.151 x PD3 + 0.043 x AD2 + 0.158 x AD3 + 0.050 × N3) - 1 if the variable is applicable, 0 if not (M: mobility, SC: self-care, UA: usual activity,, PD: pain / discomfort, AD: anxiety / depression); * Variable definition; M2: 1 if mobility is 'level 2', 0 if not; M3: 1 if mobility is 'level 3', 0 if not; SC2: 1 if self-care is 'level 2', 0 if not; SC3: 1 if self-care is 'level 3', 0 if not; UA2: 1 if usual activity is 'level 2', 0 if not; UA3: 1 if usual activity is 'level 3', 0 if not; PD2: 1 if pain / discomfort is 'level 2', 0 if not; PD3: 1 if pain / discomfort is 'level 3', 0 if not; AD2: 1 if anxiety / depression is 'level 2', 0 if not; AD3: 1 if anxiety / depression is 'level 3', 0 if not; N3: 1 if there is at least one level 3, others are 0	12 weeks